The invention relates to compositions, methods and kits for the determination of analytes such as, for example, antibodies, in samples, such as patient samples, known or suspected to contain one or more of such analytes. In some examples the invention relates more particularly to maintaining stability of receptor reagents during storage as liquid formulations at temperatures above freezing. In some examples the invention relates more particularly to enhancing the sensitivity of receptor reagents for use in assays for analytes.
The clinical diagnostic field has seen a broad expansion over the past 35 years or more, both as to the variety of materials of interest that may be readily and accurately determined, as well as the methods for the determination. Convenient, reliable and non-hazardous means for detecting the presence of low concentrations of materials in liquids is desired. In clinical chemistry these materials may be present in body fluids in concentrations below 10−12 molar. The difficulty of detecting low concentrations of these materials is enhanced by the relatively small sample sizes that can be utilized.
The need to determine many analytes in blood and other biological fluids has become increasingly apparent in many branches of medicine. In endocrinology the knowledge of plasma concentration of a number of different hormones is often required to resolve a diagnostic problem or a panel of markers for a given diagnosis where the ratios could assist in determining disease progression. Receptors such as hormone receptors are used commonly in a number of in vitro applications. In diagnostic assays, for example, receptors such as, for example, hormone receptors are used for detection of patient antibodies that are indicative of one or more disease states. In a particular example, thyrotropin (also known as thyroid-stimulating hormone or TSH) receptors are used in diagnostics assays for the detection of TSH receptor antibodies as an aid in the differential diagnosis of Graves' disease.
Due to their instability in liquid form, many receptors are either dried on a surface or lyophilized. These approaches are not desirable since they add manufacturing cost and are inconvenient for those who use the reagents. Furthermore, upon reconstitution for use, many such receptors still have a very short half-life.
There is, therefore, a continuing need to develop compositions comprising receptors that exhibit good stability in a liquid form and good sensitivity in an assay employing the receptors to measure levels of antibodies and other analytes in patients.